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Existing estimates of the costs of antimicrobial resistance exhibit broad variability, and the contributing factors are not well understood. This study examines factors that contribute to variation in these estimates.Studies of the costs of resistant infections (1995–2009) were identified, abstracted, and stated in comparable terms (eg, converted to 2007 U.S. dollars). Linear regressions were conducted to assess how costs incurred by patients with resistant infections versus those incurred by uninfected or susceptible-organism-infected controls varied according to (1) costs incurred by control subjects; (2) study population characteristics; (3) methodological factors (eg, matching); and (4) length of stay.Estimates of difference in costs incurred by patients with resistant infections versus patients without resistant infections varied between $−27,609 (control costs exceeded case costs) and $126,856. Differences were greater when the costs incurred by control subjects were higher (ie, when the underlying cost of care was high). Study-adjusted cost differences were greater for bloodstream infections (vs. any other infection site), for studies that reported median (vs. mean) costs, for studies that reported total (vs. postinfection or infection-associated) costs, for studies that used uninfected (vs. susceptible-organism-infected) controls, and for studies that did not match or adjust for length of stay before infection.The cost of antimicrobial resistance seems to vary with the underlying cost of care. Increased costs of resistance are partially explained by longer length of stay for patients with resistant infections. Further research is needed to assess whether interventions should be differentially targeted at the highest cost cases.